The objective of the proposed research is to continue the study of the interactions at the molecular level between known antineoplastic drugs and cellular macromolecules. The use of inhibitors is a potent tool for the study and understanding of basic cellular mechanisms, both normal and abnormal (malignant). It is felt that some of the more subtle differences between normal and neoplastic cells may be elucidated by comparing the effects of known anticancer drugs on these two cell types. The details of the drug-macromolecular interaction will be studied using: (1) cell-free systems, (2) simple bacterial and bacteriophage systems, (3) established mammalian cell lines, and (4) primary cultures derived from human cancers. In this way the knowledge gained using the simpler systems can be accumulated and extended to the more complex mammalian systems and ultimately to primary human cancer cells. BIBLIOGRAPHIC REFERENCES: Bearden, J.C. Jr., R.S. Lloyd, and C.W. Haidle. 1977. Bleomycin-induced breakage of closed-circular DNA. Biochem. Biophys. Res. Commun. in press. Kuo, M.T., L.T. Auger, G.F. Saunders, and C.W. Haidle. 1977. Effect of bleomycin on the synthesis and function of RNA. Cancer Res. in press.